Germline mutations in the WNK4 gene originate Gordon syndrome or pseudohypoaldosteronism type II, a
familial form of hypertension with hyperkalemia and hypercalciuria. In order to elucidate the contribution of
WNK4 genetic variants to hypertension and/or osteoporosis, we analyzed 271 control individuals and a cohort
of 448 hypertensive and 372 osteoporosis patients from the Portuguese population. Ten genetic variants were
detected in 4.3% of the population under study, none of which revealed any significant association to the
hypertension phenotype. In contrast, a rare missense alteration within exon 17 in a highly conserved arginine
residue showed a possible tendency for association to the osteoporosis group. Our data suggest that WNK4
polymorphism rs56116165 is a rare allelic variant in a candidate gene with a biological function in renal
calcium homeostasis that may contribute to a genetic predisposition to osteoporosis.